Drug Resistance Caused by Reversion Mutation
Cells carrying mutated BRCA1 or BRCA2 genes are defective in DNA repair by homologous recombination and, as a consequence, are highly sensitive to inhibitors of poly (ADP-ribose) polymerase (PARP). This provides the basis for a novel "synthetic lethal" approach to cancer therapy. We have r...
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| Veröffentlicht in: | Cancer research (Chicago, Ill.) Ill.), 2008-12, Vol.68 (24), p.10021-10023 |
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| container_issue | 24 |
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| container_title | Cancer research (Chicago, Ill.) |
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| creator | ASHWORTH, Alan |
| description | Cells carrying mutated BRCA1 or BRCA2 genes are defective in DNA repair by homologous recombination and, as a consequence, are highly sensitive to inhibitors of poly (ADP-ribose) polymerase (PARP). This provides the basis for a novel "synthetic lethal" approach to cancer therapy. We have recently shown that this sensitivity can be reversed, and resistance to PARP inhibition can be acquired by deletion of a mutation in BRCA2. Furthermore, a similar mechanism seems to be associated with carboplatin resistance in some BRCA2 mutation carriers with ovarian cancer. |
| doi_str_mv | 10.1158/0008-5472.CAN-08-2287 |
| format | Article |
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This provides the basis for a novel "synthetic lethal" approach to cancer therapy. We have recently shown that this sensitivity can be reversed, and resistance to PARP inhibition can be acquired by deletion of a mutation in BRCA2. Furthermore, a similar mechanism seems to be associated with carboplatin resistance in some BRCA2 mutation carriers with ovarian cancer.</description><identifier>ISSN: 0008-5472</identifier><identifier>EISSN: 1538-7445</identifier><identifier>DOI: 10.1158/0008-5472.CAN-08-2287</identifier><identifier>PMID: 19074863</identifier><identifier>CODEN: CNREA8</identifier><language>eng</language><publisher>Philadelphia, PA: American Association for Cancer Research</publisher><subject>Antineoplastic agents ; Biological and medical sciences ; Carboplatin - pharmacology ; Cell Line, Tumor ; Collagen Type XI - antagonists & inhibitors ; DNA Repair ; Drug Resistance, Neoplasm - genetics ; Enzyme Inhibitors - pharmacology ; Female ; Genes, BRCA1 ; Genes, BRCA2 ; Germ-Line Mutation ; Humans ; Leukemia, Myelogenous, Chronic, BCR-ABL Positive - drug therapy ; Leukemia, Myelogenous, Chronic, BCR-ABL Positive - genetics ; Medical sciences ; Neoplasms - drug therapy ; Neoplasms - genetics ; Ovarian Neoplasms - drug therapy ; Ovarian Neoplasms - genetics ; Pancreatic Neoplasms - drug therapy ; Pancreatic Neoplasms - genetics ; Pharmacology. 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This provides the basis for a novel "synthetic lethal" approach to cancer therapy. We have recently shown that this sensitivity can be reversed, and resistance to PARP inhibition can be acquired by deletion of a mutation in BRCA2. Furthermore, a similar mechanism seems to be associated with carboplatin resistance in some BRCA2 mutation carriers with ovarian cancer.</description><subject>Antineoplastic agents</subject><subject>Biological and medical sciences</subject><subject>Carboplatin - pharmacology</subject><subject>Cell Line, Tumor</subject><subject>Collagen Type XI - antagonists & inhibitors</subject><subject>DNA Repair</subject><subject>Drug Resistance, Neoplasm - genetics</subject><subject>Enzyme Inhibitors - pharmacology</subject><subject>Female</subject><subject>Genes, BRCA1</subject><subject>Genes, BRCA2</subject><subject>Germ-Line Mutation</subject><subject>Humans</subject><subject>Leukemia, Myelogenous, Chronic, BCR-ABL Positive - drug therapy</subject><subject>Leukemia, Myelogenous, Chronic, BCR-ABL Positive - genetics</subject><subject>Medical sciences</subject><subject>Neoplasms - drug therapy</subject><subject>Neoplasms - genetics</subject><subject>Ovarian Neoplasms - drug therapy</subject><subject>Ovarian Neoplasms - genetics</subject><subject>Pancreatic Neoplasms - drug therapy</subject><subject>Pancreatic Neoplasms - genetics</subject><subject>Pharmacology. Drug treatments</subject><subject>Tumors</subject><issn>0008-5472</issn><issn>1538-7445</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>2008</creationdate><recordtype>article</recordtype><sourceid>EIF</sourceid><recordid>eNpFkF1LwzAUhoMobk5_gtIbvbIzaXqa5HJ0fsFUEL0OaXoqlW6dSSvs35uyMq_y5vC858BDyCWjc8ZA3lFKZQypSOb54jUOOUmkOCJTBlzGIk3hmEwPzIScef8dvsAonJIJU1SkMuNTcrt0_Vf0jr72ndlYjHLTeyyjYheGv-h83W6il74zXQjn5KQyjceL8Z2Rz4f7j_wpXr09PueLVWyBiy6GDBRjFbUWJaWFssqWFlCk3AhVcCwkVhkAhbSSEjMlTaEQeCIBBLKM8Rm52e_duvanR9_pde0tNo3ZYNt7HSpSJlwFEPagda33Diu9dfXauJ1mVA-a9KBADwp00KRDHjSF3tV4oC_WWP63Ri8BuB4B461pKhfc1P7AJSyoVELwP7jAbo0</recordid><startdate>20081215</startdate><enddate>20081215</enddate><creator>ASHWORTH, Alan</creator><general>American Association for Cancer Research</general><scope>IQODW</scope><scope>CGR</scope><scope>CUY</scope><scope>CVF</scope><scope>ECM</scope><scope>EIF</scope><scope>NPM</scope><scope>AAYXX</scope><scope>CITATION</scope><scope>7X8</scope></search><sort><creationdate>20081215</creationdate><title>Drug Resistance Caused by Reversion Mutation</title><author>ASHWORTH, Alan</author></sort><facets><frbrtype>5</frbrtype><frbrgroupid>cdi_FETCH-LOGICAL-c537t-565911f0cce800b9c9cdc5e743a79b3eb8ef655054f88e698ab9e5328557e1613</frbrgroupid><rsrctype>articles</rsrctype><prefilter>articles</prefilter><language>eng</language><creationdate>2008</creationdate><topic>Antineoplastic agents</topic><topic>Biological and medical sciences</topic><topic>Carboplatin - pharmacology</topic><topic>Cell Line, Tumor</topic><topic>Collagen Type XI - antagonists & inhibitors</topic><topic>DNA Repair</topic><topic>Drug Resistance, Neoplasm - genetics</topic><topic>Enzyme Inhibitors - pharmacology</topic><topic>Female</topic><topic>Genes, BRCA1</topic><topic>Genes, BRCA2</topic><topic>Germ-Line Mutation</topic><topic>Humans</topic><topic>Leukemia, Myelogenous, Chronic, BCR-ABL Positive - drug therapy</topic><topic>Leukemia, Myelogenous, Chronic, BCR-ABL Positive - genetics</topic><topic>Medical sciences</topic><topic>Neoplasms - drug therapy</topic><topic>Neoplasms - genetics</topic><topic>Ovarian Neoplasms - drug therapy</topic><topic>Ovarian Neoplasms - genetics</topic><topic>Pancreatic Neoplasms - drug therapy</topic><topic>Pancreatic Neoplasms - genetics</topic><topic>Pharmacology. Drug treatments</topic><topic>Tumors</topic><toplevel>peer_reviewed</toplevel><toplevel>online_resources</toplevel><creatorcontrib>ASHWORTH, Alan</creatorcontrib><collection>Pascal-Francis</collection><collection>Medline</collection><collection>MEDLINE</collection><collection>MEDLINE (Ovid)</collection><collection>MEDLINE</collection><collection>MEDLINE</collection><collection>PubMed</collection><collection>CrossRef</collection><collection>MEDLINE - Academic</collection><jtitle>Cancer research (Chicago, Ill.)</jtitle></facets><delivery><delcategory>Remote Search Resource</delcategory><fulltext>fulltext</fulltext></delivery><addata><au>ASHWORTH, Alan</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>Drug Resistance Caused by Reversion Mutation</atitle><jtitle>Cancer research (Chicago, Ill.)</jtitle><addtitle>Cancer Res</addtitle><date>2008-12-15</date><risdate>2008</risdate><volume>68</volume><issue>24</issue><spage>10021</spage><epage>10023</epage><pages>10021-10023</pages><issn>0008-5472</issn><eissn>1538-7445</eissn><coden>CNREA8</coden><abstract>Cells carrying mutated BRCA1 or BRCA2 genes are defective in DNA repair by homologous recombination and, as a consequence, are highly sensitive to inhibitors of poly (ADP-ribose) polymerase (PARP). This provides the basis for a novel "synthetic lethal" approach to cancer therapy. We have recently shown that this sensitivity can be reversed, and resistance to PARP inhibition can be acquired by deletion of a mutation in BRCA2. Furthermore, a similar mechanism seems to be associated with carboplatin resistance in some BRCA2 mutation carriers with ovarian cancer.</abstract><cop>Philadelphia, PA</cop><pub>American Association for Cancer Research</pub><pmid>19074863</pmid><doi>10.1158/0008-5472.CAN-08-2287</doi><tpages>3</tpages><oa>free_for_read</oa></addata></record> |
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| identifier | ISSN: 0008-5472 |
| ispartof | Cancer research (Chicago, Ill.), 2008-12, Vol.68 (24), p.10021-10023 |
| issn | 0008-5472 1538-7445 |
| language | eng |
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| source | MEDLINE; American Association for Cancer Research; Elektronische Zeitschriftenbibliothek - Frei zugängliche E-Journals |
| subjects | Antineoplastic agents Biological and medical sciences Carboplatin - pharmacology Cell Line, Tumor Collagen Type XI - antagonists & inhibitors DNA Repair Drug Resistance, Neoplasm - genetics Enzyme Inhibitors - pharmacology Female Genes, BRCA1 Genes, BRCA2 Germ-Line Mutation Humans Leukemia, Myelogenous, Chronic, BCR-ABL Positive - drug therapy Leukemia, Myelogenous, Chronic, BCR-ABL Positive - genetics Medical sciences Neoplasms - drug therapy Neoplasms - genetics Ovarian Neoplasms - drug therapy Ovarian Neoplasms - genetics Pancreatic Neoplasms - drug therapy Pancreatic Neoplasms - genetics Pharmacology. Drug treatments Tumors |
| title | Drug Resistance Caused by Reversion Mutation |
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